Preterm delivery is the leading cause of perinatal morbidity and mortality in the United States. Obstetricians often give beta- sympathomimetic agents (e.g. ritodrine) to treat preterm labor, a therapy called tocolysis. Although ritodrine is relatively selective for the beta 2 receptor (e.g., uterine smooth muscle), beta 1-receptor stimulation also occurs, resulting in increased maternal heart rate and systemic vasodilation. Magnesium sulfate (MgSO4) is often given as an alternate tocolytic drug; many clinicians believe that it incurs less risk of cardiovascular side effects. Obstetrician usually avoid ritodrine in patients at risk for hemorrhage, for fear of severe hypotension. Anesthesiologists often avoid regional anesthesia in patients recently subjected to infusion of either ritodrine or MgSO4. There are few data regarding interactions between tocolysis, hemorrhage, and anesthesia. A recent study from this laboratory showed that MgSO4 significantly worsened the maternal hypotensive response to hemorrhage in gravid ewes. The specific aims of this proposal are: 1) To hemorrhage; 2) To determine whether the tachycardia response to ritodrine alters maternal and fetal hemodynamic responses to hemorrhage; 3) To study whether, and if so why, ritodrine increases the risk of hypotension with epidural anesthesia; and 4) To study whether MgSO4 increases the risk of hypotension with epidural anesthesia. Methods. In vitro studies will use the suspended isometric vascular ring model. The contractile responses of uterine and mesenteric arterial smooth muscle to various agonists, with and without MgSO4, endothelium, and indomethacin, will be examined. In vivo studies will use chronically instrumented gravid ewes. Maternal and fetal arterial catheters will permit continuous measurement of maternal and fetal systemic arterial pressures, and intermittent measurement of maternal cardiac output. An electromagnetic flow probe will allow measurement of uterine blood flow. A lumbar epidural catheter will facilitate induction of epidural anesthesia. The long-term objectives of this proposal are: 1) To elucidate mechanisms of interaction between tocolytic drugs, hemorrhage, and anesthesia; and 1) To provide an objective basis for the choice and management of tocolytic therapy in patients at risk for hemorrhage, as well as for the choice and management of anesthesia after failed tocolysis.